Comprehensive identification of <i>FGFR1-4</i> alterations in 5 557 Chinese patients with solid tumors by next-generation sequencing.

Abstract

Deregulation of fibroblast growth factor receptor (FGFR) network is common in cancer due to activating mutations, gene amplifications and chromosomal translocations. Currently, various FGFR inhibitors are being developed. In order to optimize their clinical applications, understanding the frequencies and types of <i>FGFR</i> alterations in multiple cancer types appears to be extremely important. This study characterized <i>FGFR1-4</i> alterations in solid tumors by next-generation sequencing (NGS). Between Jun. 2019 and Aug. 2020, the sequencing data of 5 557 solid tumors of diverse types in the database of Simcere Diagnostics, Inc. (Nanjing, China) were retrospectively analyzed. A panel-based NGS assay was used to detect <i>FGFR1-4</i> alterations in tumor samples. 9.2% of cancer cases had <i>FGFR1-4</i> alterations, in which gene amplifications (51.5%) and mutations (40.7%) were frequent, whereas gene rearrangements were less common (10.0%). <i>FGFR1</i> was involved in 4.6% of 5 557 cases, <i>FGFR2</i> in 2.1%, <i>FGFR3</i> in 1.6%, and <i>FGFR4</i> in 1.4%. Of patients with <i>FGFR1-4</i> alterations, <i>TP53</i>, <i>MUC16</i>, <i>NSD3</i>, <i>MYC</i> and <i>LRP1B</i> genes were the top 5 mutant genes. <i>FGFR1-4</i> aberrations occurred in almost every type of solid tumors, with the most common tumor being endometrial carcinoma (22.2%), followed by sarcoma (17.3%), breast cancer (13.2%), gastric cancer (12.2%), and more. 0.6% of cancer cases harbored <i>FGFR1-4</i> fusions, with the most common fusion partner being <i>TACC3</i>. Two cases of GBM harboring <i>FGFR3-TACC3</i> fusions were responsive to anlotinib treatment. In conclusion, <i>FGFR1-4</i> alterations are prevalent in solid tumors of diverse types, with the majority being gene amplifications and mutations. <i>FGFR1-4</i> fusions only occur in a minority of cancer cases, and those with glioblastoma harboring <i>FGFR3-TACC3</i> fusions may benefit from anlotinib.